Induction and requirement of gene expression in the anterior cingulate cortex and medial prefrontal cortex for the consolidation of inhibitory avoidance memory
Memory consolidation is a process to stabilize short-term memory, generating long-term memory. A critical biochemical feature of memory consolidation is a requirement for gene expression. Previous studies have shown that fear memories are consolidated through the activation of gene expression in the amygdala and hippocampus, indicating essential roles of these brain regions in memory formation. However, it is still poorly understood whether gene expression in brain regions other than the amygdala/hippocampus is required for the consolidation of fear memory; however, several brain regions are known to play modulatory roles in fear memory formation. Results To further understand the mechanisms underlying the formation of fear memory, we first identified brain regions where gene expression is activated after learning inhibitory avoidance (IA) by analyzing the expression of the immediately early genes c-fos and Arc as markers. Similarly with previous findings, the induction of c-fos and Arc expression was observed in the amygdala and hippocampus. Interestingly, we also observed the induction of c-fos and Arc expression in the medial prefrontal cortex (mPFC: prelimbic (PL) and infralimbic (IL) regions) and Arc expression in the anterior cingulate cortex (ACC). We next examined the roles of these brain regions in the consolidation of IA memory. Consistent with previous findings, inhibiting protein synthesis in the hippocampus blocked the consolidation of IA memory. More importantly, inhibition in the mPFC or ACC also blocked the formation of IA memory. Conclusion Our observations indicated that the formation of IA memory requires gene expression in the ACC and mPFC as well as in the amygdala and hippocampus, suggesting essential roles of the ACC and mPFC in IA memory formation.
Induction and requirement of gene expression in the anterior cingulate cortex and medial prefrontal cortex for the consolidation of inhibitory avoidance memory 1,2 1,2 1,2* Yue Zhang , Hotaka Fukushima , Satoshi Kida
Abstract Background:Memory consolidation is a process to stabilize shortterm memory, generating longterm memory. A critical biochemical feature of memory consolidation is a requirement for gene expression. Previous studies have shown that fear memories are consolidated through the activation of gene expression in the amygdala and hippocampus, indicating essential roles of these brain regions in memory formation. However, it is still poorly understood whether gene expression in brain regions other than the amygdala/hippocampus is required for the consolidation of fear memory; however, several brain regions are known to play modulatory roles in fear memory formation. Results:To further understand the mechanisms underlying the formation of fear memory, we first identified brain regions where gene expression is activated after learning inhibitory avoidance (IA) by analyzing the expression of the immediately early genes cfos and Arc as markers. Similarly with previous findings, the induction of cfos and Arc expression was observed in the amygdala and hippocampus. Interestingly, we also observed the induction of cfos and Arc expression in the medial prefrontal cortex (mPFC: prelimbic (PL) and infralimbic (IL) regions) and Arc expression in the anterior cingulate cortex (ACC). We next examined the roles of these brain regions in the consolidation of IA memory. Consistent with previous findings, inhibiting protein synthesis in the hippocampus blocked the consolidation of IA memory. More importantly, inhibition in the mPFC or ACC also blocked the formation of IA memory. Conclusion:Our observations indicated that the formation of IA memory requires gene expression in the ACC and mPFC as well as in the amygdala and hippocampus, suggesting essential roles of the ACC and mPFC in IA memory formation.
Background To form longterm memory (LTM), shortterm memory (STM) is stabilized through a process known as memory consolidation [13]. A critical biochemical feature of memory consolidation is a requirement for gene expres sion [38]. The expression of immediateearly genes (IEGs), such as cfos, Arc, and Zif268, is regulated in a neural activ itydependent manner [916]. Therefore, the expression
* Correspondence: kida@nodai.ac.jp 1 Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo 1568502, Japan Full list of author information is available at the end of the article
of IEGs has been used as a marker to identify brain regions that are activated in response to learning or memory retrieval [1720]. Moreover, the activity dependent expression of IEGs is thought to play a critical role in the formation of LTM [2125]. Genetic inhibition of transcription factor cAMPresponsive ele mentbinding protein (CREB)mediated transcription, known as a master regulator of activitydependent tran scription, blocks the consolidation of LTM [2630]. Consistently, recent genetic studies using mice have shown that the deletion of the Arc or cfos gene, both of which are targets of CREB, led to the impairment of fear and spatial memories [31,32].